This application is for a Mentored Career Development Award (K23) to support Dr. Kevin Johnson's research and training in patient-oriented research related to understanding the central mechanisms of chronic pain, addiction and their intersection. Chronic pain conditions have a tremendous societal and personal impact. The treatment of chronic pain with long-term opioids may lack efficacy and even induce hyperalgesia. Methadone maintenance is a treatment for substance abuse, but the impact of long-term methadone on pain systems is not well-characterized. Dr. Johnson has a unique educational background in biomedical engineering, psychology, neuroscience, nursing, and patient-oriented neuroscience research. He will gain further training in the conduct of research, with a specialized focus on patients with chronic low back pain (CLBP) and on patients with methadone maintenance treatment for substance abuse. The first primary research aim is to characterize the effects of long-term opioid use on pain processing, using the follow participant groups: (1) healthy controls (2) control patients with CLBP taking no opioids, (3) patients with CLBP on long-term opioids, and (4) patients with no chronic pain on long-term methadone maintenance. Dr. Johnson will utilize clinical and behavioral assessments, quantitative sensory testing, and a variety of neuroimaging techniques to address this primary aim. Didactic and individualized training in advanced neuroimaging methods and analysis will allow Dr. Johnson to apply novel approaches for detecting the effects of long-term opioid use. The second research aim is determine the effects of Transcranial Magnetic Stimulation (TMS) over prefrontal cortex on nociceptive processing in each of the participant groups. TMS is a potential therapeutic tool for treating chronic pain, and Dr. Johnson will pursue training in translation research. Ultimately, the proposed research will advance knowledge regarding the effects of long-term opioid use and the potential for TMS to become a non-opioid therapy for treating chronic pain. Through the 5 years of this award period, Dr. Johnson will gain experience leading research in a mentored environment. Building on the training and research of this award, he will apply for independent funding to further investigate current opioid treatments approaches and to develop novel therapies for managing pain.